Chemical sensors are generally known for use in a wide variety of areas such as medicine, scientific research, industrial applications and the like. Fiber optic and electrochemical approaches are generally known for use in situations where it is desired to detect and/or measure the concentration of a parameter at a remote location without requiring electrical communication with the remote location. Structures, properties, functions and operational details of fiber optic chemical sensors can be found in U.S. Pat. No. 4,577,109 to Hirschreid, U.S. Pat. No. 4,785,814 to Kane, and U.S. Pat. No. 4,842,783 to Blaylock, as well as Seitz, "Chemical Sensors Based on Fiber Optics," Analytical Chemistry, Vol. 56, No. 1, January 1984, each of which is incorporated by reference herein.
Publications such as these generally illustrate that it is known to incorporate a chemical sensor into a fiber optic waveguide, an electrochemical gas sensor or the like, in a manner such that the chemical sensor will interact with the analyte. This interaction results in a change in optical properties, which change is probed and detected through the fiber optic waveguide or the like. These optical properties of chemical sensor compositions typically involve changes in colors or in color intensities. In these types of systems, it is possible to detect particularly minute changes in the parameter or parameters being monitored in order to thereby provide especially sensitive remote monitoring capabilities. Chemical sensor compositions that are incorporated at the distal end of fiber optic sensors are often configured as membranes that are secured at the distal tip end of the waveguide device or optrode.
Sensors of this general type are useful in monitoring the pH of a fluid, measuring gas concentrations such as oxygen and carbon dioxide, and the like. Ion concentrations can also be detected, such as potassium, sodium, calcium and metal ions.
A typical fiber optic pH sensor positions the sensor material at a generally distal location with the assistance of various different support means. Support means must be such as to permit interaction between the pH indicator and the substance being subjected to monitoring, measurement and/or detection. With certain arrangements, it is desirable to incorporate membrane components into these types of devices. Such membrane components must possess certain properties in order to be particularly advantageous. Many membrane materials have some advantageous properties but also have shortcomings. Generally speaking, the materials must be biocompatible, hemocompatible for use in the bloodstream, selectively permeable to hydrogen ions, and of sufficient strength to permit maneuvering of the device without concern about damage to the sensor.
It is also desirable to have these membrane materials be photocurable (such that curing is neater, can be done more rapidly, on a smaller scale, and directly on the optical fiber), resistant to shear forces (e.g., as present in a bloodstream), and compatible with different substrates, such that there is a choice of fiber optic materials which can be used to fabricate the sensor. It is also preferred, clearly, that a signal of sufficient intensity be produced, such that measurement is as accurate as is reasonably possible. The optical pH sensors which are currently available are frequently inadequate with regard to one or more of the aforementioned criteria.
It is additionally desired that the materials used for the sensor membrane be constructed such that pH values in a relatively wide range may be accurately measured. To date, this has not been the case with optical pH sensors. Rather, indicator compositions of prior art optical sensors typically display an apparent pKa which is substantially lower than is desirable for the accurate and precise measurement of a pH above about 7.0, e.g., as is true for the physiological pH range.
The present invention is addressed to novel fluorescent copolymer compositions which have been found to be particularly suitable for use as membranes and membrane-like components in an optical pH sensor and which provide for optical sensors which meet each of the above-mentioned criteria. That is, optical sensors as provided herein tend to adhere well to different types of substrates, eliminating in some cases the need to silanize the substrate surface, provide for superior signal intensity, are quite hemocompatible relative to prior art compositions, are rapidly cured with light, and are resistant to shear forces such as those present in flowing blood. Additionally, the novel polymer compositions are such that their apparent pKa may be raised or lowered at will, enabling measurement of a wide range of pH values in a fluid sample. It is preferred that the apparent pKa of the compositions be in the range of approximately 6.6 to 8.0, more preferably in the range of approximately 7.2 to 7.8, most preferably in the range of approximately 7.2 to 7.4, such that pH values in the physiological range may be precisely determined.